The present invention relates to a composition having an effect of alleviating symptoms associated with depression and mental and emotional stress.
A. Zanotti et al. report that the oral administration of phosphatidylserine extracted from bovine brain to aged rats with memory deficits for 12 weeks improved the performance of the aged rats (A. Zanotti et al., Psychopharmacology Berl., Vol. 99, P. 316, 1989).
Monteleoni et al., (Eur. J. Clin. Pharmacology, 385-388, 1992) investigated the chronic administration of brain cortex phosphatidylserine on the neuroendocrine responses to physical stress. The study showed that oral administration of phosphatidylserine at 800 mg per day for 10 days prior to exercise, reduced the ACTH and cortisol responses to physical exercise. A 400 mg per day dose was shown to produce no effect on the cortisol response.
Monteleoni et al. further reported (Neuroendocrinology, 52, 243-248, 1990) on the influence of brain cortex phosphatidylserine on the neuroendocrine and neurovegetative responses to physical stress. In a double blind study, every participant received intravenously brain cortex phosphatidylserine or a placebo before starting a physical exercise. Blood samples were collected before and after the exercise for plasma ACTH, cortisol and growth hormone readings. It outcome showed that in the placebo group the physical stress induced an increase in ACTH, cortisol and growth hormone while the phosphatidylserine group showed a reduction in production of ACTH and cortisol.
In a series of patents (PCT No. PCT/IL97/00147 Sec. 371 Date Feb. 24, 1999 Sec. 102(e) Date Feb. 24, 1999 PCT Filed May 6, 1997 PCT Pub. No. WO97/41874 PCT Pub. Date Nov. 13, 1997, Priority Number(s): IL19960118180 19960508; WO1997IL00147 19970506) phosphatidic acid has been shown to alleviate withdrawal symptoms associated with addiction (cigarettes, alcohol, narcotics).
REFERENCES
A. Zanotti et al, xe2x80x9cChronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged ratsxe2x80x9d, Psychopharmacology, 99, 316-321, 1989.
Monteleone, et al., xe2x80x9cBlunting by chronic phosphatidylserine administration of the stress-induced activation of the bypothalamo-pituitary-adrenal axis in healthy menxe2x80x9d, Eur. J. Clin. Pharmacology, 385-388, 1992.
Monteleone, et al., xe2x80x9cEffects of Phosphatidylserine on the Neuroendocrine Response to Physical Stress in Humansxe2x80x9d, Neuroendocrinology, 52, 243-284, 1990.
Eibl A. and Kovatchev S. xe2x80x9cPreparation of phospholipids analogs by phospholipase D.xe2x80x9d (xe2x80x9cMethods in Enzymologyxe2x80x9d Vol. 72, pages: 632-639, 1981).
Faraj, B. A., Olkowski, Z. L., Jackson, R. T. Expression of a high-affinity serotonin transporter in human lymphocytes. Int. J. Immunopharm. 16, 561-567, 1994.
Faraj, B. A., Olkowski, Z. L., Jackson, R. T. Binding of [3H]-dopamine to human lymphocytes: possible relationship to neurotransmitter uptake sites. Pharmacology, 42, 134-141, 1991.
Owens, M. J., Nemeroff, C. B., xe2x80x9cRole of serotonin in the pathophysiology of depression: focus on the serotonin transporterxe2x80x9d. Clin. Chem. 40, 288-295, 1994.
PCT No. PCT/IL97/00147 Sec. 371 Date Feb. 24, 1999 Sec. 102(e) Date Feb. 24, 1999 PCT Filed May 6, 1997 PCT Pub. No. WO97/41874 PCT Pub. Date Nov. 13, 1997, Priority Number(s): IL19960118180 19960508; WO1997IL00147 19970506
It is an object of the present invention to provide an improver having an effect of alleviating symptoms associated with depression and mental and emotional stress.
According to the research work of the present inventors, it is confirmed that a complex of phosphatidyl-L-serine and phosphatidic acid produced by an enzymatic conversion utilizing phospholipase-D of at least one raw material lecithin selected from the group consisting of soybean lecithin, rapeseed lecithin, and egg yolk lecithin, has in mental and emotional stress and depression a prominent effects of decreasing cortisol blood level and serotonin uptake to normal level.
An improver of the present invention contains phosphatidyl-L-serine and phosphatidic acid or the salt thereof as the effective ingredient, wherein the phosphatidyl-L-serine and phosphatidic acid have a structural fatty acid chain derived from at least one raw material lecithin selected from the group consisting of soy bean lecithin, rapeseed lecithin, and egg yolk lecithin.
The improver of the present invention may be administered effectively via intravenous administration and oral administration. The improver may be mixed with other excipients such as additional phospholipids and lyso-phospholoipids, sugar and protein to prepare capsules and granules with improved handling and shelf life. Because of the absence of any safety problem, the improver may be blended into daily foods and beverages, either in powder or liquid form or as hydrogenated substance for use in improving and preventing mental and emotional stress and depression symptoms.
The aforementioned phosphatidyl-L-serine and phosphatidic acid as the effective ingredients in accordance with the present invention are both produced by the enzymatic reaction with phospholipase-D using as the substrate soy bean lecithin, rapeseed lecithin or egg yolk lecithin.
The process will now be illustrated. A raw material lecithin (namely, phosphatidylcholine) selected from soy bean lecithin, rapeseed lecithin and egg yolk lecithin is subjected to the process of transphosphatidylation and hydrolysis with phospholipase-D in the presence of L-serine and water, thereby substituting the choline group with the serine group or the hydroxyl group, to produce the rearranged phosphatidyl-L-serine and phosphatidic acid.
Any commercially available soy bean lecithin, rapeseed lecithin or egg yolk lecithin may be used, with no limitation, as the raw material. As phospholipase-D for use in the process of enzymatic conversion, use may be made of for example those from cabbage and actinomyces, if they have an activity on lecithin or hydrogenated lecithin or lysolecithin in the presence of L-serine and water to produce phosphatidyl-L-serine and phosphatidic acid.
A specific process of enzymatic conversion is known and described in for example the article by Eibl A. and Kovatchev S. xe2x80x9cPreparation of phospholipids analogs by phospholipase-D.xe2x80x9d (xe2x80x9cMethods in Enzymologyxe2x80x9d Vo. 72, pages: 632-639, 1981), so no detailed explanation is described herein.